1. Field of the Invention
The present invention relates to a process for manufacturing a highly pure acarbose, and particularly to a process which uses alcohol for precipitation and separation, and a strong cation exchange chromatography and an immobilized enzyme affinity chromatography for manufacturing a highly pure acarbose to treat diabetes.
2. Description of the Related Art
Acarbose,
O-4,6-Dideoxy-[[[1S-(1α,4α,5α,6α)]-4,5,6,-trihydroxy-3-(hydroxymethyl)-2-c yclohexen-1-yl]amino]-α-D-glucopyranosyl-(1→4)-O-α-D-glucopyranosyl-(1→4)-D-glucose,C25H43NO18,Mw 645.63, is an oligo-derivative. Acarbose inhibits the activity of α-glucosidase at the edge of the small intestine by invertibility for slowly turning complex carbohydrates and disaccharide into glucose, which can be absorbed by humans, to decrease concentration of triglycerol and insulin in blood and blood sugar.
In the early 1970s, acarbose could improve the ratio of meat and fat, so it was used as an additive in feed for animals such as pigs. Recently, researches have found that acarbose controls the blood sugar of NIDDM and decreases the insulin value after eating, for preventing diabetic carbiovascular complications. However, acarbose cannot directly change insulin resistance. Acarbose only has a few aftereffects, such as abdominal distension, borborygums and diarrhea, which go away after a period of treatment, and hardly affect health. The glucobay of the Bayer was first approved in 1995 by FDA. So far, acarbose is primarily manufactured using Actinoplanes sp. or Streptomyces glaucescens. 
The DOH of Taiwan adjusts the adjusting blood sugar material to be health food. Further, Easterners eats polysaccharide which differs from the fat eaten by Westerners. Therefore, acarbose not only treats diabetes, but can also be used in diet food.
U.S. Pat. No. 4,062,950 sets forth a recover and purification process for manufacturing acarbose, and discloses that acarbose-containing fermentation broth is discolored by anion resins or activated carbons in the acidic condition, and that acarbose are absorbed by activated carbons in the neutral condition and are eluted by ethyl alcohol solution or acetone solution in the acidic condition. The elute passes through the cation exchange chromatography, and acarbose are finally washed by the acid or base solution. The eluted liquid is counteracted and concentrated in the vacuum, and acarbose with 85% purity is precipitated by the organic solvent. The high purity of the acarbose can be manufactured if the exchange chromatography uses celluloses as a matrix. Further, the liquid is concentrated and precipitated by the organic solvent to get a highly pure acarbose. The process is complicated because the process must use activated carbons for absorbing and the exchange chromatography process repeated many times for purification of acarbose.
U.S. Pat. No. 4,174,439 mixes cation and anion exchange resin into acarbose-containing fermentation broth to absorb acarbose and elutes the acarbose by deionized water. The carbose solution is processed twice by a cation and anion exchange resin and is eluted by hydrochloric acid, and is processed with a neutralizing treatment by an anion exchange resin and frozen until dry to acarbose with 52-58% purity.
Further, U.S. Pat. No. 4,666,776 and U.S. Pat. No. 4,767,850 improve U.S. Pat. No. 4,174,439 to use strong cation exchange resin, be washed by hydrochloric acid, be processed by a neutralizing treatment with an anion exchange resin and frozen until dry to get acarbose with 79-82% purity.
The above methods of purifying the acarbose all repeat the anion and cation exchange chromatography to get the acarbose solution and finally use cation exchange chromatography to get a high concentration of acarbose. However, it is difficult to achieve a purity of acarbose sufficient for use as a medical drug.
U.S. Pat. No. 4,904,769 discloses a method in which impure acarbose passes through a weak cation exchange chromatography containing carbonyl, cellulose, and dextran with specific temperature and pH values to get acarbose with a 90% purity. The process is complicated and uses a weak ion exchange chromatography in an expansive process, resulting in high manufacturing costs.
Finally, WO 99/07720 discloses taking an impure acarbose manufactured by U.S. Pat. No. 4,174,439, U.S. Pat. No. 4,666,776 and U.S. Pat. No. 4,767,850, which passes through a strong cation exchange chromatography containing non-aromatic to get highly pure acarbose, and the processes are typically complicated with high manufacturing costs.